Alzheimers Attack On Brain May Be Enabled By Nerve Protein
The findings, in test tube experiments and in mice, appear to solve a mystery about how a substance called beta amyloid links to nerve cells in the brain and disrupts their ability to communicate.
The study, published today in the journal Nature, gives scientists at drug companies and universities a new target for Alzheimers. The results are likely to kick off a competition to find a medicine to treat the disease, which robs some 20 million people around the world of their memory and mental ability.
“The race will be to find the drug that blocks that receptor and protects the nerve cell,” said Sam Gandy, associate director of the Alzheimers Disease Research Center at Mount Sinai School of Medicine in New York and a scientific adviser to the Alzheimers Association. If the findings are confirmed, “this would immediately provide a new target, a new way to screen for new drugs that would otherwise have been totally undiscoverable.”
Researchers have been trying to understand the workings of Alzheimers disease ever since 1906, when Alois Alzheimer, a German pathologist, dissected the brain of a deceased patient and described the massive cellular damage he found.
Interference With Nerve Cells
In recent years, most researchers have come to believe that this damage is caused by clumps of the beta amyloid protein gathering around nerve cells and interfering with their ability to communicate.
One gap in that theory is that scientists hadnt offered an explanation as to how beta amyloid interacts with cells. The new study, led by Stephen Strittmatter, a Yale neurology professor, suggests that the small protein, known as a prion, acts as a receptor that allows beta amyloid to link to it and send signals into the cell.
Until now, prions have mostly been known for their role in mad cow disease. A toxic, misshapen form is linked to the human version of the illness, known as Creutzfeldt-Jakob disease. The form of the prion protein studied in the Alzheimers paper is normal and is found on the surface of nerve cells.
Lead Suspect
“Cellular prion protein has now emerged as the lead suspect,” said Lennart Mucke, an Alzheimers researcher and director of the Gladstone Institute for Neurological Disease in San Francisco, in a telephone interview yesterday. Strittmatters findings suggest that scientists could design a drug that would block the prion from binding to the nerve cell.
The goal of such a drug would be to prevent the beta amyloid clumps from attaching to the neurons and starting a “toxic cascade that prevents memory function,” said Strittmatter. “If you can do that, you can halt the disease.”
They sent electrical currents between groups of neurons that had been extracted from mice and exposed to beta amyloid. Some of the mice had been engineered to lack the prion protein and others hadnt. In the mice that lacked the prion protein, the beta amyloid had no effect on the flow of electrical current, suggesting beta amyloid isnt damaging without the prion protein.
Next Studies
The next step is to test the impact of the prion protein on living mice, Strittmatter said. He and his colleagues are mating mice engineered to lack the prion with others engineered to have a version of Alzheimers disease.
“Do the offspring preserve memory in spite of fact that they carry human Alzheimers disease genes?” Strittmatter asked. His hope is that “even though theyre making bad forms of amyloid beta, it has no place to attach to the neuron and do its bad thing.”
These studies are under way, and it will take at least six months to see if the mice will begin to show symptoms of the disease or be spared because they lack the prion, Strittmatter said.